Navigation Links
Origin of inherited pain disorder pinpointed

The genetic basis for a rare inherited disorder that causes severe burning pain with no warning has been pinpointed by researchers. They found that paroxysmal extreme pain disorder (PEPD) is caused by specific mutations in porelike sodium channels in peripheral nerve cells—a discovery that they said emphasizes the role of such channel disorders in inflammatory pain. Such findings of abnormal function in disease also provide insights into the normal function of such channels, they said.

R. Mark Gardiner, of University College London, and his colleagues published their findings in the December 7, 2006, issue of the journal Neuron, published by Cell Press.

So-called "voltage-gated sodium channels" are central to the neuron's ability to propagate a nerve impulse. In response to voltage changes in a nerve cell caused by a nerve impulse, these channels snap open, allowing sodium to flow across the cell membrane, further propagating the nerve impulse. Rapid, precise activation and inactivation is key to their normal operation.

In their studies, the researchers sought to understand the basis of PEPD, which is characterized by abrupt paroxysms of pain in the rectum, eye, and jaw. They first performed a detailed genetic comparison of affected and unaffected members of one large family that showed inheritance of the disease. That analysis revealed that mutations that compromise the gene for a component of one particular sodium channel, called SCN9A, were the likely culprit. Further analysis of the gene in 11 affected families and two sporadic cases, indeed, revealed that mutations in SCN9A are responsible for the disease in at least two-thirds of PEPD cases.

Analysis of these mutations revealed that they all disrupted the ability of the sodium channel to rapidly snap shut, prolonging activation of the peripheral nerves in which the channels functioned. What's more, the researchers found, the drug carbamazepine—known to be effective in PEPD—act s to correct this abnormality in cultures of neurons.

The researchers also compared PEPD with another inherited pain disorder, primary erythermalgia (PE) that is not alleviated by carbamazepine. PE is also caused by mutations in SCN9A and is characterized by pain in the extremities triggered by exercise or temperature change. In contrast to PEPD, which is caused by mutations that disrupt inactivation the sodium channel, PE arises from mutations that lower its activation threshold.

The researchers concluded that their findings "further emphasize the critical role of [this sodium channel] in human inflammatory pain and explain the differential drug sensitivity of PEPD and PE."


Source:Cell Press

Related biology news :

1. International Team Determines Geographic Origin of Leprosy
2. New Look at DNA Hints at Origin of UV Damage
3. Stem Cells Found In Cerebellum; Possible Cell of Origin for Childhood Brain Tumors
4. Researchers Discover Ancient Origins Of Tuberculosis-causing Bacteria
5. Genetic therapy reverses nervous system damage in animal model of inherited human disease
6. Tendency to hair loss inherited from the mother
7. Gene therapy cures inherited liver disease in rats
8. Cell therapy slows progression of an inherited neurological disease; Improves motor skills in mice
9. Early-stage immune system control of HIV may depend on inherited factors
10. Association of herpesvirus with lung disorder questioned
11. Newly discovered virus linked to childhood lung disorders and Kawasaki disease
Post Your Comments:

(Date:4/13/2017)... SANTA MONICA, Calif. , April 13, 2017 /PRNewswire/ ... New York will feature emerging and ... Innovation Summits. Both Innovation Summits will run alongside the ... variety of speaker sessions, panels and demonstrations focused on ... east coast,s largest advanced design and manufacturing event will ...
(Date:4/11/2017)... 11, 2017 No two people are ... the New York University Tandon School of Engineering ... found that partial similarities between prints are common ... mobile phones and other electronic devices can be ... vulnerability lies in the fact that fingerprint-based authentication ...
(Date:4/5/2017)... April 5, 2017 Today HYPR Corp. ... the server component of the HYPR platform is officially ... the end-to-end security architecture that empowers biometric authentication across ... has already secured over 15 million users across the ... of connected home product suites and physical access represent ...
Breaking Biology News(10 mins):
(Date:10/10/2017)... (PRWEB) , ... October 10, 2017 , ... Dr. Bob ... at his local San Diego Rotary Club. The event entitled “Stem ... CA and had 300+ attendees. Dr. Harman, DVM, MPVM was joined by two ...
(Date:10/10/2017)... ... October 10, 2017 , ... The Pittcon ... awards honoring scientists who have made outstanding contributions to analytical chemistry ... Pittcon 2018, the world’s leading conference and exposition for laboratory science, which will ...
(Date:10/9/2017)... Phoenix, Arizona (PRWEB) , ... October 09, 2017 ... ... of Kindred, a four-tiered line of medical marijuana products targeting the needs of ... production and packaging of Kindred takes place in Phoenix, Arizona. , As operators ...
(Date:10/7/2017)... , Oct. 6, 2017  The 2017 ... of three scientists, Jacques Dubochet, Joachim Frank ... developments in cryo-electron microscopy (cryo-EM) have ... within the structural biology community. The winners worked ... can now routinely produce highly resolved, three-dimensional images ...
Breaking Biology Technology: